CA2318579C - Nitrogen-containing heterocyclic compounds and medicaments containing the compounds - Google Patents

Nitrogen-containing heterocyclic compounds and medicaments containing the compounds Download PDF

Info

Publication number: CA2318579C
Authority: CA; Canada
Prior art keywords: group; compound; ring; salt; alkyl
Prior art date: 1998-01-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA002318579A

Other languages

English (en)

French (fr)

Other versions

CA2318579A1 (en

Inventor

Kazuki Miyazaki

Yasutaka Takase

Takao Saeki

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eisai R&D Management Co Ltd

Original Assignee

Eisai R&D Management Co Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-01-26

Filing date

1999-01-21

Publication date

2008-11-25

1999-01-21 Application filed by Eisai R&D Management Co Ltd filed Critical Eisai R&D Management Co Ltd

1999-07-29 Publication of CA2318579A1 publication Critical patent/CA2318579A1/en

2008-11-25 Application granted granted Critical

2008-11-25 Publication of CA2318579C publication Critical patent/CA2318579C/en

2019-01-21 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

-1 Nitrogen-containing heterocyclic compounds Chemical class 0.000 title claims abstract description 217
150000001875 compounds Chemical class 0.000 title claims description 193
239000003814 drug Substances 0.000 title abstract description 16
125000001424 substituent group Chemical group 0.000 claims abstract description 101
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 59
150000003839 salts Chemical class 0.000 claims abstract description 51
125000005843 halogen group Chemical group 0.000 claims abstract description 42
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 39
125000002252 acyl group Chemical group 0.000 claims abstract description 29
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 19
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 15
125000005842 heteroatom Chemical group 0.000 claims abstract description 15
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 15
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 14
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 13
229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
229930195735 unsaturated hydrocarbon Natural products 0.000 claims abstract description 10
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 9
229930195734 saturated hydrocarbon Natural products 0.000 claims abstract description 9
125000004434 sulfur atom Chemical group 0.000 claims abstract description 9
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims abstract description 8
125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims abstract description 8
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 8
125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims abstract description 7
125000002029 aromatic hydrocarbon group Chemical group 0.000 claims abstract 2
238000004519 manufacturing process Methods 0.000 claims description 83
150000002430 hydrocarbons Chemical group 0.000 claims description 17
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 14
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 13
125000003277 amino group Chemical group 0.000 claims description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 9
150000004945 aromatic hydrocarbons Chemical group 0.000 claims description 9
125000000000 cycloalkoxy group Chemical group 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
230000002401 inhibitory effect Effects 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 claims description 7
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
229940095074 cyclic amp Drugs 0.000 claims description 7
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
206010012601 diabetes mellitus Diseases 0.000 claims description 5
125000000168 pyrrolyl group Chemical group 0.000 claims description 5
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
206010040047 Sepsis Diseases 0.000 claims description 4
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
102100040247 Tumor necrosis factor Human genes 0.000 claims description 4
108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims description 4
102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 4
LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
201000006417 multiple sclerosis Diseases 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
229910052710 silicon Inorganic materials 0.000 claims description 4
239000010703 silicon Substances 0.000 claims description 4
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical group O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 4
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 3
208000023275 Autoimmune disease Diseases 0.000 claims description 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
208000009329 Graft vs Host Disease Diseases 0.000 claims description 3
208000001132 Osteoporosis Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
206010003246 arthritis Diseases 0.000 claims description 3
208000006673 asthma Diseases 0.000 claims description 3
230000001684 chronic effect Effects 0.000 claims description 3
125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
208000024908 graft versus host disease Diseases 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 2
125000006596 (C1-C3) alkylcarbonyloxy group Chemical group 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 2
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
YMQHTLXPDXLYRH-UHFFFAOYSA-N 6,7-diethoxy-n-methyl-4-[3-(5-methylsulfanylpyridin-3-yl)phenyl]quinazolin-2-amine Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC(NC)=NC=1C(C=1)=CC=CC=1C1=CN=CC(SC)=C1 YMQHTLXPDXLYRH-UHFFFAOYSA-N 0.000 claims description 2
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 2
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 2
125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims description 2
229910052787 antimony Inorganic materials 0.000 claims description 2
WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 claims description 2
125000005110 aryl thio group Chemical group 0.000 claims description 2
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
229910052797 bismuth Inorganic materials 0.000 claims description 2
JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 2
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
CFBGXYDUODCMNS-UHFFFAOYSA-N cyclobutene Chemical compound C1CC=C1 CFBGXYDUODCMNS-UHFFFAOYSA-N 0.000 claims description 2
ZXIJMRYMVAMXQP-UHFFFAOYSA-N cycloheptene Chemical compound C1CCC=CCC1 ZXIJMRYMVAMXQP-UHFFFAOYSA-N 0.000 claims description 2
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 2
229910052732 germanium Inorganic materials 0.000 claims description 2
GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 claims description 2
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 claims description 2
GUVXZFRDPCKWEM-UHFFFAOYSA-N pentalene Chemical compound C1=CC2=CC=CC2=C1 GUVXZFRDPCKWEM-UHFFFAOYSA-N 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
229910052698 phosphorus Inorganic materials 0.000 claims description 2
239000011574 phosphorus Substances 0.000 claims description 2
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 2
229960002317 succinimide Drugs 0.000 claims description 2
125000003396 thiol group Chemical class [H]S* 0.000 claims description 2
125000005505 thiomorpholino group Chemical group 0.000 claims description 2
229910052718 tin Inorganic materials 0.000 claims description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 2
CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 claims 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical group C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims 1
ZERMCEQVELTHIA-UHFFFAOYSA-N 3-chloro-n-[3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl]-4-methoxybenzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC(NC)=NC=1C(C=1)=CC=CC=1NC(=O)C1=CC=C(OC)C(Cl)=C1 ZERMCEQVELTHIA-UHFFFAOYSA-N 0.000 claims 1
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical group C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims 1
DKDFWWKBGJKAKN-UHFFFAOYSA-N 6,7-diethoxy-n-methyl-4-(3-quinolin-3-ylphenyl)quinazolin-2-amine Chemical compound C1=CC=CC2=CC(C=3C=CC=C(C=3)C=3N=C(NC)N=C4C=C(C(=CC4=3)OCC)OCC)=CN=C21 DKDFWWKBGJKAKN-UHFFFAOYSA-N 0.000 claims 1
NUFYHZZBROBBPA-UHFFFAOYSA-N 6,7-diethoxy-n-methyl-4-[3-(5-methylsulfinylpyridin-3-yl)phenyl]quinazolin-2-amine Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC(NC)=NC=1C(C=1)=CC=CC=1C1=CN=CC(S(C)=O)=C1 NUFYHZZBROBBPA-UHFFFAOYSA-N 0.000 claims 1
HLJSDHUIAYEBMD-UHFFFAOYSA-N 6,7-dimethoxy-n-methyl-4-(3-quinolin-3-ylphenyl)quinazolin-2-amine Chemical compound C1=C(OC)C(OC)=CC2=NC(NC)=NC(C=3C=C(C=CC=3)C=3C=C4C=CC=CC4=NC=3)=C21 HLJSDHUIAYEBMD-UHFFFAOYSA-N 0.000 claims 1
MDRWEPCUTBAODM-UHFFFAOYSA-N 6,7-dimethoxy-n-methyl-4-[3-(5-methylsulfinylpyridin-3-yl)phenyl]quinazolin-2-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC(NC)=NC=1C(C=1)=CC=CC=1C1=CN=CC(S(C)=O)=C1 MDRWEPCUTBAODM-UHFFFAOYSA-N 0.000 claims 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
OOXWYYGXTJLWHA-UHFFFAOYSA-N cyclopropene Chemical compound C1C=C1 OOXWYYGXTJLWHA-UHFFFAOYSA-N 0.000 claims 1
DDTGNKBZWQHIEH-UHFFFAOYSA-N heptalene Chemical compound C1=CC=CC=C2C=CC=CC=C21 DDTGNKBZWQHIEH-UHFFFAOYSA-N 0.000 claims 1
XLPYHPJKKYWWSK-UHFFFAOYSA-N n-[3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl]-3,4-dimethoxybenzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC(NC)=NC=1C(C=1)=CC=CC=1NC(=O)C1=CC=C(OC)C(OC)=C1 XLPYHPJKKYWWSK-UHFFFAOYSA-N 0.000 claims 1
PEXGIDOBAGZKTG-UHFFFAOYSA-N n-[3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl]-6-(methylamino)pyridine-3-carboxamide Chemical compound C1=NC(NC)=CC=C1C(=O)NC1=CC=CC(C=2C3=CC(OC)=C(OC)C=C3N=C(NC)N=2)=C1 PEXGIDOBAGZKTG-UHFFFAOYSA-N 0.000 claims 1
IAKJILRHARQNJN-UHFFFAOYSA-N n-[3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl]pyridine-4-carboxamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC(NC)=NC=1C(C=1)=CC=CC=1NC(=O)C1=CC=NC=C1 IAKJILRHARQNJN-UHFFFAOYSA-N 0.000 claims 1
229910052760 oxygen Inorganic materials 0.000 claims 1
239000001301 oxygen Substances 0.000 claims 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical group C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
239000011593 sulfur Substances 0.000 claims 1
229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 abstract description 17
239000002587 phosphodiesterase IV inhibitor Substances 0.000 abstract description 17
125000004432 carbon atom Chemical group C* 0.000 abstract description 14
150000004677 hydrates Chemical class 0.000 abstract description 14
229910052799 carbon Inorganic materials 0.000 abstract description 6
125000001183 hydrocarbyl group Chemical group 0.000 abstract 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
238000005160 1H NMR spectroscopy Methods 0.000 description 104
239000013078 crystal Substances 0.000 description 103
101150041968 CDC13 gene Proteins 0.000 description 100
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 100
239000002904 solvent Substances 0.000 description 55
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
238000006243 chemical reaction Methods 0.000 description 42
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 37
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
229940093499 ethyl acetate Drugs 0.000 description 35
235000019439 ethyl acetate Nutrition 0.000 description 35
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
239000000203 mixture Substances 0.000 description 31
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
229910052739 hydrogen Inorganic materials 0.000 description 26
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
239000012043 crude product Substances 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
239000000047 product Substances 0.000 description 20
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 19
239000012267 brine Substances 0.000 description 19
238000000034 method Methods 0.000 description 19
238000010898 silica gel chromatography Methods 0.000 description 19
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 16
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
239000012046 mixed solvent Substances 0.000 description 14
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
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230000000144 pharmacologic effect Effects 0.000 description 1
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical group C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
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XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
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125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical group N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
XJYYTJSLGQZIJU-UHFFFAOYSA-N pyridin-3-yloxyboronic acid Chemical compound OB(O)OC1=CC=CN=C1 XJYYTJSLGQZIJU-UHFFFAOYSA-N 0.000 description 1
RVQZKNOMKUSGCI-UHFFFAOYSA-N pyridine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC=NC=C1 RVQZKNOMKUSGCI-UHFFFAOYSA-N 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical group C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
150000003246 quinazolines Chemical class 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000012121 regulation of immune response Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
125000005920 sec-butoxy group Chemical group 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
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239000002002 slurry Substances 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000004317 sodium nitrate Substances 0.000 description 1
235000010344 sodium nitrate Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
229940032094 squalane Drugs 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
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239000003826 tablet Substances 0.000 description 1
239000003760 tallow Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000010998 test method Methods 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
230000007704 transition Effects 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
102000003390 tumor necrosis factor Human genes 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
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210000003462 vein Anatomy 0.000 description 1
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238000013293 zucker diabetic fatty rat Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Diabetes (AREA)
Pulmonology (AREA)
Obesity (AREA)
Rheumatology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Hematology (AREA)
Oncology (AREA)
Pain & Pain Management (AREA)
Transplantation (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Dermatology (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Quinoline Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA002318579A 1998-01-26 1999-01-21 Nitrogen-containing heterocyclic compounds and medicaments containing the compounds Expired - Fee Related CA2318579C (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
JP10013062A JPH11209350A (ja)	1998-01-26	1998-01-26	含窒素複素環誘導体およびその医薬
JP10-13062		1998-01-26
PCT/JP1999/000215 WO1999037622A1 (en)	1998-01-26	1999-01-21	Nitrogenous heterocyclic derivatives and medicine thereof

Publications (2)

Publication Number	Publication Date
CA2318579A1 CA2318579A1 (en)	1999-07-29
CA2318579C true CA2318579C (en)	2008-11-25

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Family Applications (1)

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CA002318579A Expired - Fee Related CA2318579C (en)	1998-01-26	1999-01-21	Nitrogen-containing heterocyclic compounds and medicaments containing the compounds

Country Status (9)

Country	Link
US (2)	US6352989B1 (da)
EP (1)	EP1052254B1 (da)
JP (2)	JPH11209350A (da)
AT (1)	ATE512955T1 (da)
CA (1)	CA2318579C (da)
DK (1)	DK1052254T3 (da)
ES (1)	ES2367413T3 (da)
PT (1)	PT1052254E (da)
WO (1)	WO1999037622A1 (da)

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MY134008A (en) *	1999-12-22	2007-11-30	Merck Frosst Canada Inc	Subtituted 8-arylquinoline phospohodiestrase-4 inhibitors
US6410563B1 (en)	1999-12-22	2002-06-25	Merck Frosst Canada & Co.	Substituted 8-arylquinoline phosphodiesterase-4 inhibitors
DE10043667A1 (de) *	2000-09-05	2002-03-14	Merck Patent Gmbh	2-Guanidino-4-aryl-chinazoline
HRP20030507A2 (en)	2000-12-20	2005-06-30	Merck & Co. Inc.	Process for making substituted 8-arylquinolinium benzensulfonate
US6740666B2 (en) *	2000-12-20	2004-05-25	Merck & Co., Inc.	Substituted 8-arylquinoline phosphodiesterase-4 inhibitors
US7074801B1 (en) *	2001-04-26	2006-07-11	Eisai Co., Ltd.	Nitrogen-containing condensed cyclic compound having a pyrazolyl group as a substituent group and pharmaceutical composition thereof
WO2002088079A2 (en) *	2001-05-01	2002-11-07	Bristol-Myers Squibb Company	Dual inhibitors of pde 7 and pde 4
AR038658A1 (es)	2001-06-15	2005-01-26	Novartis Ag	Derivados de 4-aril-2(1h) quinazolinona y 4-aril-quinazolina 2-sustituidas, un proceso para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la preparacion de un medicamento
GB0128109D0 (en) *	2001-11-23	2002-01-16	Astrazeneca Ab	Therapeutic use
GB0209715D0 (en) *	2002-04-27	2002-06-05	Astrazeneca Ab	Chemical compounds
CA2504820C (en) *	2002-11-06	2011-08-23	Grelan Pharmaceutical Co., Ltd.	Pyrazolonaphthyridine derivatives
GB0230015D0 (en)	2002-12-23	2003-01-29	Novartis Ag	Organic compounds
US7144911B2 (en)	2002-12-31	2006-12-05	Deciphera Pharmaceuticals Llc	Anti-inflammatory medicaments
US7279576B2 (en)	2002-12-31	2007-10-09	Deciphera Pharmaceuticals, Llc	Anti-cancer medicaments
US7202257B2 (en)	2003-12-24	2007-04-10	Deciphera Pharmaceuticals, Llc	Anti-inflammatory medicaments
JP2006523638A (ja) *	2003-04-16	2006-10-19	エフ．ホフマン−ラ　ロシュ　アーゲー	キナゾリン化合物
MXPA05011523A (es) *	2003-04-30	2006-01-23	Inst For Pharm Discovery Inc	Heteroarilos sustituidos como inhibidores de proteinas de tirosina fosfatasas.
US20070099938A1 (en) *	2003-10-24	2007-05-03	Ono Pharmaceutical Co., Ltd.	Antistress drug and medical use thereof
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1999
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- 1999-01-21 AT AT99900654T patent/ATE512955T1/de active
- 1999-01-21 PT PT99900654T patent/PT1052254E/pt unknown
- 1999-01-21 CA CA002318579A patent/CA2318579C/en not_active Expired - Fee Related
- 1999-01-21 JP JP2000528546A patent/JP4132666B2/ja not_active Expired - Fee Related
- 1999-01-21 US US09/600,995 patent/US6352989B1/en not_active Expired - Lifetime
- 1999-01-21 DK DK99900654.7T patent/DK1052254T3/da active
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ATE512955T1 (de)	2011-07-15
EP1052254A4 (en)	2008-03-05
EP1052254B1 (en)	2011-06-15
US6800644B2 (en)	2004-10-05
ES2367413T3 (es)	2011-11-03
US6352989B1 (en)	2002-03-05
EP1052254A1 (en)	2000-11-15
JP4132666B2 (ja)	2008-08-13
US20020055516A1 (en)	2002-05-09
CA2318579A1 (en)	1999-07-29
DK1052254T3 (da)	2011-09-12
PT1052254E (pt)	2011-09-05
JPH11209350A (ja)	1999-08-03
WO1999037622A1 (en)	1999-07-29

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